Abstract 12195: Novel Magnetic Resonance Imaging Marker of Myocardial Fibrosis: Validation in a Model of Hypertensive Heart Disease
BACKGROUND The relative distribution volume of gadolinium measured by post-contrast CMR T1 imaging, closely correlates with the myocardial extracellular volume fraction (MECVF). MECVF may be a novel marker of diffuse interstitial fibrosis, not quantifiable by late gadolinium enhancement imaging. We hypothesized that MECVF correlates with the connective tissue volume fraction (CTVF) in a rodent model of hypertensive heart disease created by chronic inhibition of nitric oxide biosynthesis with Nω-nitro-L-arginine-metyl-ester (L-NAME).
METHODS L-NAME (40mg/Kg/day) or placebo were administered respectively to 22 (body weight 36.9±2.3g) and 15 (body weight 37.6±2.5g) wild-type mice. 4.7T CMR studies were done at baseline and 7 weeks after treatment. The myocardial partition coefficient was measured by before and after Gd-DPTA (0.5 mmol/kg) T1 quantification by Look-Locker gradient-echo cine and adjusted to hematocrit to measure MECVF. CTVF was obtained by Masson's trichrome staining. The heart of L-NAME-treated mice showed hypertrophy (weight indexed LV mass 2.2±0.3 vs. 4.1±0.4 μg/g for placebo, p<0.001) and increased CTVF (2.58%±0.6 vs. 8.6%±1.5 for placebo, P<0.001) consistent with hypertensive heart disease. MECVF was substantially higher in L-NAME-treated mice (0.267 vs. 0.414 for placebo, p<0.001). MECVF only increased significantly from baseline to 7-weeks in animals treated with L-NAME (p<0.001). MECVF strongly correlated with CTVF and with weight-indexed LV mass (both r=0.85, p<0.0001), and also correlated with LVEF (r=0.48, p=0.01). Preliminary data from our group using an analogous CMR protocol confirmed similar adverse myocardial remodeling in 10 hypertensive patients without evidence of CAD, compared to 9 healthy controls (MECVF 0.34 vs. 0.24, p<0.0001).
CONCLUSION MECVF quantification by CMR is a robust measure of myocardial extracellular matrix expansion and interstitial fibrosis in a hypertensive heart disease model. MECVF correlates with CTVF, determined by histology. This novel MRI-based index may become useful to assess early adverse myocardial remodeling in several cardiac conditions manifesting by myocardial fibrosis.
- © 2011 by American Heart Association, Inc.